BJA Advance Access published online on June 19, 2007
British Journal of Anaesthesia, doi:10.1093/bja/aem135
Remifentanil–midazolam sedation for paediatric patients receiving mechanical ventilation after cardiac surgery
1 Anaesthesia Research Group, Peninsula Medical School, Plymouth, UK
2 Department of Pharmacy, Derriford Hospital, Plymouth, UK
3 Bristol Royal Children's Hospital, Bristol, UK
4 United Bristol Healthcare Trust, Bristol, UK
5 Department of Medical Physics, United Bristol Healthcare Trust, Bristol, UK
6 Department of Anaesthesia and Critical Care, University of Bristol, Bristol, UK
* Corresponding author. E-mail: robert.sneyd{at}pms.ac.uk
Background: Sedation of critically ill children requiring artificial ventilation remains a therapeutic challenge due to large individual variation in drug effects and a paucity of knowledge of pharmacokinetics in this population. This study aimed to determine the pharmacokinetics of remifentanil in children requiring ventilation after cardiac surgery.
Methods: Twenty-six ventilated children aged 1 month to 9.25 yr (median 1.77 yr) who had undergone cardiac surgery were sedated with a fixed rate infusion of midazolam 50 µg kg–1 h–1 and a remifentanil infusion that was commenced at 0.8 µg kg–1 min–1 for a minimum of 60 min and subsequently decreased by 0.1 µg kg–1 min–1every 20 min until the patient awoke. Arterial blood concentrations of remifentanil and midazolam were measured using high-performance liquid chromatography. Mixed-effects population models were fitted to the remifentanil concentration–time data.
Results: Satisfactory sedation was achieved in all patients as assessed by Comfort score during the initial maintenance and reduction phase of the remifentanil infusion. One patient was withdrawn from the study due to hypotension. Remifentanil pharmacokinetics were best described using a two-compartment allometric model. For a typical child with a body weight of 10.5 kg, clearance was 68.3 ml kg–1 min–1, intercompartmental clearance was 80 ml kg–1 min–1, the central compartment volume was 91.7 ml kg–1, and the peripheral compartment volume was 141 ml kg–1.
Conclusions: A combination of remifentanil and midazolam provided satisfactory sedation for these patients. Owing to enhanced clearance rates, smaller (younger) children will require higher remifentanil infusion rates than larger (older) children and adults to achieve equivalent blood concentrations.
Keywords: analgesics opioid, remifentanil; children; hypnotics benzodiazepines, midazolam; pharmacokinetics remifentanil; sedation
Presented in part at the Anaesthetic Research Society Summer Meeting, Sheffield, UK, July 2005 (Br J Anaesth 2005; 95: 578P–9P), and at Euroanaesthesia, Madrid, June 2006 (Eur J Anaesthesiol 2006; 23(S37): 171).